Dissecting lysosomal viscosity fluctuations in live cells and liver tissues with an ingenious NIR fluorescent probe.

ABSTRACT

Viscosity is a pivotal component in the cell microenvironment, while lysosomal viscosity fluctuation is associated with various human diseases, such as tumors and liver diseases. Herein, a near-infrared fluorescent probe (BIMM) based on merocyanine dyes was designed and synthesized for detecting lysosomal viscosity in live cells and liver tissue. The increase in viscosity restricts the free rotation of single bonds, leading to enhanced fluorescence intensity. BIMM exhibits high sensitivity and good selectivity, and is applicable to a wide pH range. BIMM has near-infrared emission, and the fluorescent intensity shows an excellent linear relationship with viscosity. Furthermore, BIMM possessing excellent lysosomes-targeting ability, and can monitor viscosity changes in live cells stimulated by dexamethasone, lipopolysaccharide (LPS), and nigericin, and differentiate between cancer cells and normal cells. Noticeably, BIMM can accurately analyze viscosity changes in various liver disease models with HepG2 cells, and is successfully utilized to visualize variations in viscosity on APAP-induced liver injury. All the results demonstrated that BIMM is a powerful wash-free tool to monitor the viscosity fluctuations in living systems.